The comprehensive regionalization of natural resources directly reflects the spatial heterogeneity of complex natural resources of land, minerals, forests, grasslands, wetlands, waters, islands, and so on. It provides an important scientific basis for the construction of the national natural resources observation system and the spatial distribution of scientific field observation stations by zones, categories, and levels. At present, theoretical research on the comprehensive regionalization of natural resources in China is still lacking. Furthermore, a scientific and accurate evaluation paradigm for its technical methods has not been formed. First, based on the spatial pattern and dynamic characteristics of natural resources, and starting with the systematic management of mountain, water, forest, cropland, and grassland systems, this article presented a conceptual framework for the comprehensive regionalization of natural resources. Next, we developed an indicator system and technical methods for the comprehensive regionalization of natural resources according to the basic principles of subjectivity, integrality, multiple scale, hierarchy, and expansibility. Finally, we examined the differences between the comprehensive regionalization of natural resources and natural system and ecological regionalization. This study may help enhance our knowledge of the coupling relationship and differentiation characteristics of natural resources, promote multidisciplinary development, and serve the requirements of the national strategies including the system of natural resource management.